I describe an experimental approach for analysis of the circuitry that regulates the expression of the enzyme alcohol dehydrogenase (ADH) in Drosophila. My laboratory has worked with this particular system because ADH is a relatively simple protein; because it is obtainable in high yields; because it is readily purifiable; because it shows interesting tissue specificities and developmental variations; and because mutations, revertants, and recombinants at the Adh-locus are selectable by chemical mass screening procedures. Five distinct sub-proposals are presented. In the first, I propose to continue working to generate a large number of mutations in ADH. Secondly, my laboratory will characterize these mutants by a variety of techniques. Thirdly, we will decide whether these mutations are in the ADH structural locus by virtue of their intracistronic map position, and by virtue of changes in their peptide composition. Fourthly, we will try to generate "transregulatory" mutants in which the regulatory elements of one gene will control the structural locus of ADH. Finally, we will look for suppressors of ADH-negatives in an effort to further describe the nature of regulatory loci. BIBLIOGRAPHIC REFERENCES: Alcohol Dehydrogenase Negative Mutants in Drosphila: Defects at the Structural Locus? By Marcia Schwartz and William Sofer. Accepted for publication in Genetics (1976). Chemical Selection of Mutants that Affect ADH Activity in Drosophila. III. Effects of Ethanol. By Charles Vigue and William Sofer. Accepted for publication in Biochemical Genetics (1976).